DCs in Immune Tolerance in Steady-State Conditions

  • Tomohiro Fukaya
  • Hideaki Takagi
  • Honami Taya
  • Katsuaki Sato
Part of the Methods in Molecular Biology book series (MIMB, volume 677)


Dendritic cells (DCs) are antigen-presenting cells (APCs) characterized by a unique capacity to stimulate naïve T cells and initiate primary immune responses. Recent studies suggest that DCs are also involved in the induction of immunological tolerance in peripheral tissues under steady-state conditions by maintaining the homeostasis of self-reactive CD4+Foxp3+naturally occurring thymic-derived regulatory T cells (nTregs) and de novo generation of antigen-specific CD4+Foxp3+inducible regulatory T cells (iTregs). We demonstrate here the impact of CD11+DCs on the antigen-specific differentiation of CD4+Foxp3+iTregs from CD4+Foxp3T cells under steady-state and inflammatory conditions. CD11c+DCs promoted the transforming growth factor (TGF)-β1-mediated conversion of CD4+Foxp3T cells into CD4+Foxp3+iTregs in vitro, while stimulation of CD11c+DCs with CpG oligodeoxynucleotide (ODN) abrogated this conversion. Furthermore, antigen-specific generation of CD4+Foxp3+iTregs required the function of CD11+DCs under steady-state conditions, whereas such conversion was severely abolished under inflammatory conditions. Thus, these results suggest the crucial role of DCs in the antigen-specific de novo conversion of CD4+Foxp3T cells into CD4+Foxp3+iTregs under steady-state conditions, thereby leading to the establishment of peripheral immune tolerance.

Key words

Dendritic cells Tolerance Regulatory T cells Steady-state conditions Inflammatory conditions 



The author would like to thank Yumiko Sato, Kaori Sato, Kawori Eizumi, and Naomi Uchimura for excellent technical assistance. This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan (c) 17790334 and 19590505 (K.S.).


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Copyright information

© Humana Press 2010

Authors and Affiliations

  • Tomohiro Fukaya
    • 1
  • Hideaki Takagi
    • 1
  • Honami Taya
    • 1
  • Katsuaki Sato
    • 1
  1. 1.Laboratory for Dendritic Cell ImmunobiologyRIKEN Research Center for Allergy and ImmunologyKanagawaJapan

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